This project is concerned with construction or improvement of methodology for the computer simulation of metabolic systems, analysis of the properties of completed models, and construction of new models. The principal methodological efforts will be in improving the efficiency of simulating multi-enzyme (and consequently also single-enzyme) models, including faster solution of differential equations, and in faster and more convenient methods of getting initial estimates for such solutions. We will particularly try to implement an efficient method of building and representing models involving both compartmentation and metabolism, where the experimental measurements are of radioactivity, and to apply this to construction of neurochemical models involving the Krebs cycle, related amino acids, and neurotransmitters. We will also simulate gluconeogenesis in rat liver, primarily as a multi-enzyme problem, possibly also as a radioactivity problem as described above, and will give some attention to systematic extraction of information from these and other existing models. BIBLIOGRAPHIC REFERENCES: J.W. London, L.M. Shaw, D. Fetterolf, and D. Garfinkel, A Mechanism and Kinetic Constants for Hog Kidney and Human Serum Gamma-Glutamyl Transferase. Fed. Proc. 35, 1497 (1976). D. Garfinkel, M.J. Achs, M.C. Kohn, J. Phifer, G.-C. Roman, Construction of More Reliable Metabolic Models Without Repeated Solution of the Differential Equations Composing Them. Proc. Summer Computer Simulation Conference, July 12-14, 1976, Washington, D.C., 493-9 (1976).